anti- convulsants Flashcards
What are neurotransmitter receptors?
proteins
What do neurotransmitter receptors match?
match the size & shape of a neurotransmitter
How are neurotransmitter receptors named?
named according to the transmitter they bind with
neurotransmitters are ______________ or ______________ depending on the type of receptor it bind to
inhibitory or excitatory
What neurotransmitters are inhibitory?
- dopamine
- serotonin
- GABA
What neurotransmitters are excitatory?
- acetylcholine (ACH)
- norepinephrine
Where is acetylcholine (ACH) found?
found in CNS, PNS, & ANS
is ACH excitatory or inhibitory?
can be either excitatory or inhibitory depending on the neurons secreting it
Is ACH excitatory or inhibitory in the parasympathetic nervous system?
excitatory at neuromuscular junction
is ACH excitatory or inhibitory in the autonomic nervous system?
inhibitory; slows HR
What is serotonin (5-hydroxytryptamine) derived from?
derived from tryptophan
Where is serotonin primarily found?
- GI tract
- platelets
- brainstem
What feeling does serotonin contribute to?
contributes to feeling of well being & mood regulation
Where is dopamine mainly located?
in the substantia nigra of midbrain/basal ganglia region
What does dopamine control?
- behavior & cognition
- volutary motor movement
- motivation & punishment
- reward & attention
- memory
- learning
What neuropsychiatric & voluntary motor movement disorders is dopamine involved in?
- social phobia
- ADHD
- SUD
- parkininsons
- tourettes
What is the chief inhibitory transmitter in the CNS?
gamma amino butyric acid (GABA)
What effect does GABA have on the brain?
relaxing, antianxiety & aniconvulsant effect on brain
What effect does GABA have on the muscles?
inhibitory effect on muscles (decrease muscle spasm & improve tone)
What is norepinephrine in the brain?
an excitatory neurotransmitter in the brain
What is norepinephrine in the endocrine system?
a stress hormone within the endocrine system
What part of the nervous system is norepinephrine a part of?
sympathetic nervous system
what does norepinephrine play a role in?
plays a role in fight or flight response
What is glutamate a major mediator of?
major mediator of excitatory signal
What functions is glutamate involved in?
- cognition
- memory
- learning
What is action potential (neuron conduct impulses)?
- abrupt changes in membrane potential which permit nerve signals to be transmitted from the cell body down the axon
- stimulated sodium, potassium, & calcium ions to move across axon membrane
In what state are neurons usually?
polarized (negatively charged state)
What happens when a neuron receives a signal?
it becomes positively charged & this increase in positive charge sens the message down the nerve
What are the three phases of action potential?
- depolarization of the neuron = positively charged ion
- repolarization of neuron = return of neuron to a negative value
- resting period
What impulses can lead to seizures?
impulses that do not maintain a systematic order (excitatory, inhibitory, & rest phase become irregular & chaotic) can lead to seizures
What is a seizure?
a single episode of abnormal electrical discharge from cortical neurons that results in an abrupt & temporary altered state
What is epilepsy?
a group od syndromes characterized by unprovoked, recurrent seizures
What is status epillepticus?
continuous seizure activity for more than 5 minutes or 2 or more sequential seizures that occur without full recovery of consciousness between attacks
What are the common causes of seizures?
trauma
ETOH withdrawal
illicit drug use
brain tumor
congenital malformations
stroke
metabolic disorders
- uremia, electrolyte imbalance
alzheimers
neurodegenerative disease
idiopathic
What can trigger a seizure?
- flashing lights
- stress
- certain drugs
- metabolic changes
What are the 5 common causes of epilepsy?
genetic causes
head trauma
medical disorders
prenatal injury
developmental disorders
What should we know about genetic causes of epilepsy
> 30 mutated genes have been found in families with epilepsy
- may occur in genes coding for different things (ex. ion channels, neuronal receptors, transcription factors)
- many pediatric epilepsies are associated w/ randon gene mutation for the first time (de novo)
- about half of seizure disorders, no genetic or structural abnormality is present
What medical disorders can cause epilepsy?
- dementia
- meningitis
- encephalitis
What developmental disorders can cause epilepsy?
- autism
- down syndrome
how do seizures work?
- messages from the body are carried by the neurons (nerve cells) of the brain through discharges of electrochemical energy
- these impulses occur in bursts
- during periods of unwanted discharges, parts of the body may act erratically
What is needed for an actual seizure to occur?
- excitable neurons
- increased excitatory glutaminergic activity
- reduction in activity of normal inhibitory GABa projection
Who can have a seizure?
anyone!
what are the two classifications of seizures?
focal or partial
generalized
what are the two kinds of focal or partial seizures?
simple partial
complex partial
What are the types of generalized seizures?
absence (petit mal)
tonic-clonic (grand mal)
atonic/akinetic (drop attacks)
status epilepticus
Where in the brain are focal seizures?
start 7 remain in 1 hemisphere
In focal seizures there are _____- ___________ burst of action potentials 7 ____________________
high- frequency; hypersynchronization (large number of neurons dire action potentials together)
what do focal seizure affect?
sensory & motor function
autonomic sx
automatism
What are the autonomic sx of focal seizures?
due to stimulation of ANS
- pallor
- sweating
- pupillary dilation
- epigastric sensation
What is automatism?
coordinated involuntary movements occuring during state of impaired consciousness either during or after seizure. Pt is unaware, often associated with temporal seizures
Is pt aware or unaware in focal seizures?
awareness can be maintained or lost
do pts have aura with focal seizures?
some may experience a warming sensation before seizure
What are characteristics of focal seizures when pt retains awareness?
- no impairment of consciousness
- similar to partial seizures
- may have movement of body parts
- may experience an aura
What are characteristics of a focal seizure when awareness is altered?
- impairment of consciousness
- spreads to both hemispheres
What are characteristics of partial seizures?
- begins in part of one hemisphere (typically in the temporal lobe)
- may be simple or complex
In what part of the brain does a generalized seizure occur?
- start in 1 hemisphere & spreads w/ involvement of both hemisphere
- affects both hemispheres of the brain
do generalized seizures have motor sx?
may have motor and/or nonmotor sx
is consciousness maintained or impaired in generalized seizures?
impairment of consciousness
What occurs in a tonic-clonic seizure (grand mal)?
begin with rigid violent contractions (tonic) followed by repetitive clonic activity of all extremities; body stiffness & relaxation
What are tonic seizures characterized by?
- muscle stiffness
- dilation of pupils
- altered respirations
- usually less than a minute
what are absence seizures characterized by?
short episodes of staring & loss of consciousness
- last around 10 seconds
What are myoclonic seizures characterized by?
- bilateral jerking of muscles
- no loss of consciousness
What are atonic seizures characterized by?
- sudden loss of muscle tone causing a person to collapse or drop to the ground
is status epilepticus an emergency?
yes; a neurological emergency
What does status epilepticus need?
requires immediate intervention because of the extreme energy expenditure & potential lack of oxygen during prolonged seizures
how is a seizure dx?
H & P
neurological exam
diagnostic procedures
What diagnostic procedures are used to dx a seizure?
- chemistries/ blood work for toxins to check for drug-related causes
- toxicology screen
- CT/MRI to r/o structural causes like tumors
- EEG to measure brain rhythms & to capture abnormal brain activity during a seizure
What are the three phase of a seizure?
pre-ictal
ictal
post-ictal
What is the pre-ictal phase of a seizure?
when seizure may be started by a trigger and/or preceded by an aura
What happens during the ictal phase of a seizure?
- actual seizure
- increases in metabolic demand
What happens in the post-ictal phase?
- has decreased responsiveness
- feels fatigue
What is important to do during the post-ictal phase?
keep pt safe & monitor their recovery
What are anticonvulsants also known as?
antiepileptic drugs (AED)
What are indications for anticonvulsants?
- used for long term management of chronic epilespsy
- management of seizures not caused by epilepsy
- off-label uses
What are the off-label uses for anticonvulsants?
- anxiety
- bipolar disorder
- chronic pain
- migraines
What is selection of medication for tx based on?
classification of seizures & epilepsy
- broad spectrum
- narrow-spectrum
What are broad spectrum anticonvulsants used for?
effective for tx of focal & generalized seizure
What are narrow spectrum anticonvulsants used for?
used primarily for focal- onset seizures (including focal which evolve to b/l convulsive seizures)
What are the factors that are evaluated when selecting an anticonvulsant medication?
- efficacy
- tolerability
- presence of comorbidites
- pharmacokinetic profile
- potential drug-drug interactions
- ease of use
- cost
-age - gender
list examples of anticonvulsants that work as NA+ channel blockers?
- carbamazepine
- oxcarbazepine (trileptal)
- eslicarbazepine
- felbamate
- lamotrigine
- lacosamide ( vimpat)
- phenytoin & fosphenytoin(IV)
- topiramate
- valproate
- rufinamide
list examples of anticonvusants that work as glutamate receptor blockers?
- topiramate
- zonisamide (zonegran)
- perampanel
- felbate
- levetiracetam
- brivaracetam (PO, IV only > 16 yo)
list examples of anticonvusants that work as calcium channel blockers?
- ethosuximide
- gabapentin
- lamotrigine (lamictal)
- pregabalin
- valproic acid
- zonisamide
list examples of anticonvusants that work as GABA enhancers?
- benzodiazepines
- barbiturates
- valproic acid (depakote)
- gabapentin
- pregabalin
- ethosuximide
How do meds that block sodium channels work?
- prevent return of the channel to active state; stabilizes them; inactive state
- prevent repetitive firing
How do meds that block calcium channels work?
- calcium going in during cells resting state facilities development of an action potential
- inhibits slow depolarization which is needed for spike-wave bursts
- these meds help to “lock the channel”
How do meds that enhance GABA work?
- may enhance Cl- influx which makes cell more negative and harder for cell to generate action potential
- some decrease metabolism of GABA so more is available
How do meds that block glutamate work?
- bind glutamate which is an excitatory neurotransmitter
- glutamate receptor has 5 potential binding sites
anticonvulsants are to __________ seizures; not ____
control; cure
What is the anticonvulsant prescribed based on?
type of seizure
What do many anticonvulsants require?
blood monitoring
What patient education should be given related to anticonvulsants?
- take as precribed
- never stop taking on own
- side effect management
What class is phenytoin a part of?
sodium channel blocker
How does phenytoin work?
- works to stabilize the neurons from becoming too excited
- stops the spread of seizure activity in the motor cortex
phenytoin is _______ (90%) protein- bound meaning it has a higher risk for ______ _____________
highly; drug interactions
What are indications for Phenytoin?
tonic- clonic seizures
status epilepticus
prophylaxis for surgery
What is the therapeutic range for phenytoin?
10-20mcg/ml; very narrow therapeutic range
What should you monitor in pts taking phenytoin?
peak & troughs
What are the routes of administration for phenytoin?
PO, IM, & IV
What are precautions for giving IV phenytoin?
- infuse over 30-60 minutes
- can be very irritating to veins
What should you do for those taking phenytoin & on tube feeds?
need to stop tube feed for 2 hrs before & after giving med
What are the side effects of phenytoin?
neurologic
- drowsiness
- ataxia
- irritability
- visual problems
- peripheral neuropathy
- N/V
- headache
cardiovascular
- hypotension
- arrhythmias
skin
- rash
- steven- johnsons syndrome
other
- suicidal thoughts
- gingival hyperplasia (gum overgrowth)
How does phenobarbital work?
inactivates fast sodium channels leading to enhanced GABA effects & decreased glutamate release
What class is phenobarbital in?
barbiturates
What is the half-life of phenobarbital?
very long half-life
What are the side effects of phenobarbital?
- sedation
- respiratory depression
- diplopia (double vision)
- cognitive skill impairment
- hypotension
- hyperactivity & inattention in children
What can phenobarbital cause?
physical dependence
What is carbamazepine’s mechanism of action similar to?
phenytoin
What class does carbamazepine belong to?
sodium channel blockers
What types of seizures is carbamazepine used for?
- used for several different types of seizures
- drig of choice for partial & generalized tonic-clonic seizures
- avoid in absence or myoclonic seizures as it may worsen them
Carbamazepine inhibits the spread of __________ activity
seizures
Where should carbamazepine be kept?
needs to be kept in a dry location (not a bathroom)
for what disorders is carbamazepine used off-label?
- trigeminal neuralgia
- bipolar disorder
What does carbamazepine interact with?
oral contraceptives; reducing their effectiveness
What labs should be performed when taking carbamazepine?
CBC (esp. WBC)
drug levels
sodium
CBC
LFTs
BUN/Cr (esp in those with renal impairment)
What is the therapuetic level of carbamazepine?
4-12 mcg/ml
What are side effects of carbamazepine?
- rash
- steven johnson syndrome
- increased SI
- headache
- diplopia
- ataxia
- drowsiness
- sedation
- N/V
- hyponatremia
- decreased blood counts (neutropenia & thrombocytopenia)
should carbamazepine be taken with or without food?
take with food
What should you never do when taking carbamazepine?
stop abruptly
oxycarbazepine has the same efficacy as _________________, but is better tolerated
carbamazepine
What does oxycarbazepine work as?
a sodium channel blocker
When is oxycarazepine used?
used as adjunctive therapy or monotherapy for partial seizures in children & adults
With what seizures should oxycarbazepine not be used?
absence & myoclonic because it may worsen them
oxycarbazepine decreases efficacy of _____ _______________
oral contraceptives
What can oxycarbazepine increase the risk of?
suicidal ideations
How does valproic acid/ valproate work?
inactivation of fast sodium channels; GABA enhancer
What are the indications for valproic acid?
- absence seizures
- myoclonic seizures
- tonic-clonic seizures
- partial seizures
- neonatal seizures
When is valproic acid used off-label?
used to contol sx of acute mania in bipolar disorder
What can valproic acid be given with?
phenytoin
What are the side effects of valproic acid?
- N/V
- sedation/ dizziness
- pancreatitis
- increased ammonia levels
- thrombocytopenia (monitor CBC)
- suicidal thoughts
- liver toxicity
What should you monitor with a pt on valproic acid?
monitor CBC
monitor LFTs
check therapeutic levels
What is the therapeutic level of valproic acid?
50-100 mcg/ml; narrow therapeutic range
Should valproic acid be taken with or without food?
taken with food
How should IV valproic acid be given?
- must be diluted with at least 50ml NSS or D5W
- give over an hour (no more than 20mg/min)
What should you avoid with valproic acid?
avoid sudden withdrawal
How does gabapentin work?
thought to act on calcium channels to decrease glutamate & increase GABA in the brain
What are indications for gabapentin?
partial seizures
new onset epilepsy
with what seizures should gabapentin not be given?
myoclonic seizures; may worsen them
What are the off- label uses for gabapentin?
- chronic neuropathic pain
- anxiety
- hot flashes/night sweats
- headaches
- hiccups
- alcohol withdrawal
What are the side effects of gabapentin?
- fatigue (often given at night)
- mental cloudiness
- leukopenia
- edema
- weight gain
- emotional lability
- tremors
- GI side effects
- suicidal thoughts
What should you do for renal patients taking gabapentin?
reduce dose in renal patients
when should gabapentin be used cautiously?
cautious use in those with an addiction history
Do you need to monitor drug levels for gabapentin?
no
how should you stop gabapentin?
withdrawal slowly
When will gabapentin doses be very high?
doses will be very high for pain control
